Vessel wall defects

 

Vessel wall defects are infrequently seen in veterinary medicine and can be inherited or acquired.

Inherited

Inherited defects involving the vessel wall include Ehlers-Danlos and Marfan’s syndrome.

Ehlers-Danlos syndrome

Ehlers-Danlos syndome, also called cutaneous asthenia (“rubber puppy disease”), is an uncommon, inherited connective tissue disorder characterized by loose, hyperextensible, fragile skin. This defect has been recognized in both dogs and cats as well as in humans, mink, cows, sheep and horses. The underlying defect is in the synthesis and/or maturation of type I collagen and as a result of lack of vascular support, affected animals often experience subcutaneous hematomas and have long bleeding times. Human patients with Ehlers-Danlos syndrome can also be symptomatic, with mild clinical signs (e.g. bruising, excessive menstrual bleeding) to fatal bleeds in specific subtypes (there are several different subtypes, including classic, dermatospararaxis, hypermobile, and vascular, with the latter having the most severe clinical manifestation). Symptoms are largely attributed to “fragile” vessels, which rupture readily, however there is data to support hemostatic defects, particularly defects in platelet function (secretion and/or aggregation to ADP, collagen or thrombin-related activation peptide), which were identified in at least 80% of one study of 141 patients (with various subtypes, most common of which were the classic or hypermobile forms). The presence of platelet function defects increased the odds ratio of bleeding symptoms in this cohort (Artoni et al 2018).

Marfan’s syndrome

Marfan’s syndrome is a genetic defect in fibrillin in humans and cattle. The animals develop aneurysms, usually involving the aorta and pulmonary artery, and die from massive bleed-outs secondary to aneurysmal rupture.

Acquired

Vasculitis can be due to infectious or immune-mediated causes. Vasculitis can result in thrombocytopenia due to local platelet aggregate formation or can initiate disseminated intravascular coagulation.

Infectious causes

Rickettsia rickettsii, the etiologic agent of Rocky Mountain Spotted Fever (RMSF), is an obligate intracellular parasite transmitted principally by the vector ticks Dermacentor variabilis and Dermacentor andersoni. The organism invades vascular endothelial cells leading to cell necrosis, increased vascular permeability, and perivascular hemorrhage and edema. The developing vasculitis is accompanied by thrombocytopenia and variable activation of the coagulation mechanism. Early signs may include petechial and ecchymotic hemorrhages of the skin and mucous membranes, retinal hemorrhage, epistaxis, melena, and hematuria. Severely affected individuals may develop DIC. The most useful test for diagnosing RMSF is serologic testing. Although cross reactions do develop between other rickettsial organisms, the titer is usually highest for the specific rickettsia causing the infection. Paired acute and convalescent serum samples (10 to 14 days apart) are recommended for testing. Tetracycline is the recommended therapy. Intravenous fluid therapy should also be used with caution due to the presence of increased vascular permeability. Although the incidence is sporadic, herpesvirus infection can result in the rapid death of puppies usually between the ages of 7 and 21 days. The disease is characterized by multiple hemorrhages throughout numerous tissues including the liver, kidney, brain, gastrointestinal tract and lung as a consequence of a viral-induced necrotizing vasculitis. Puppies usually die within 24 hours; treatment is often unsuccessful.

Immune-mediated vasculitis

Deposition of immune complexes in small vessels can cause damage to the wall with perivascular leakage of plasma and blood cells that mimics thrombocytopenia. The antigens involved in the complexes can be autoantigens or antigens of infectious agents. Petechial and ecchymotic hemorrhages and marked edema of affected areas are typical signs. The most well known syndrome in domestic animals is purpura hemorrhagica of horses. This syndrome is one of acute onset of edema of the head and limbs with petechiae in the mucous membranes. The syndrome is usually a sequela of infectious diseases; many affected horses have recently had Strangles (Streptococcus equi var equi infection). Horses with purpura hemorrhagica have normal platelet counts. A necrotizing vasculitis has been reported in young Beagle and Bernese Mountain dogs. Thrombocytopenia is variable in these disorders.

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